Education is very essential, particularly in this era of globalization. Rapid advances in science and information technology have been made in many spheres of life. Each person must adjust to changing circumstances. Therefore, abilities are required to assist with this condition. Creative thinking is one competence that is possessed. This study aimed to assess the creative thinking capacity of students who employ the Bio-Entrepreneurship (BEP) learning approach. This study used a quasi-experiment with a non-equivalent control group design. The study consisted of a population of 138 class XII MIPA students at SMA Negeri 4 Parepare. Through purposive sampling, 67 students were selected as the sample, with 33 in the control group and 34 in the experimental class group. The tools used for data collection were observation sheets and creative thinking ability tests. Data analysis used descriptive and inferential analysis, which included homogeneity tests, hypothesis tests, and normality. The result showed that the experimental group had an average creative thinking ability value of 70,569, and the control group was 65,965. The calculated t-value (4.889) exceeded the critical t-value (1.998) with a significance level of 0.00 < 0.05. So, there is a significant difference between the creative thinking abilities of students who taught with and without using the Bio-Entrepreneurship (BEP) approach in biotechnology material for class XII of SMA Negeri 4 Parepare. The implications of this study can strengthen the theory that the BEP approach can significantly improve students' creative thinking abilities and provide benefits for students, teachers, and researchers themselves in implementing and applying different learning approaches than before, especially in enhancing creative thinking abilities.